Overview of HPPD, HMS, and CloR. a The reactions catalyzed by HPPD, HMS, and CloR. The stereochemistry of the initial CloR hydroxylation has not been defined. b Overlays of the crystal structures of Fe-HPPD (carbons in green, PDB ID: 1CJX) aligned with Co-HMS bound to 4-hydroxymandelate (carbons in aqua, PDB ID: 2R5V). Given the sequence divergence of CloR from structurally characterized proteins, CloR did not yield high-confidence homology models from I-TASSER [125] and is therefore omitted. c A proposed mechanism for catalysis by HPPD, HMS, and the first oxidative decarboxylation by CloR. For details and discussion, see the text. d A mechanistic proposal for the second oxidative decarboxylation by CloR. A concerted β-scission mechanism is shown in red. ET = electron transfer